The regulation of LIV‐1 mRNA in MDA‐MB‐231 human breast cancer cells and its association with E‐cadherin

Abstract

LIV‐1 is an estrogen‐regulated gene encoding a member of the ZIP family of zinc transporters (SLC39A6). It is expressed in both estrogen‐receptor positive and negative breast cancer cells. In estrogen‐receptor positive MCF‐7 breast cancer cells, LIV‐1 expression is induced by both estrogen and insulin. LIV‐1 has also been observed to induce the expression of the cell adhesion protein E‐cadherin, thought to play a role in metastasis. In the present study, we investigated the regulation of LIV‐1 and its relationship to E‐cadherin in MDA‐MB‐231estrogen‐receptor negative breast cancer cells. Cells were treated with insulin and EGF for 24 h and the mRNA concentrations of LIV‐1 and E‐cadherin were analyzed by RT‐PCR. EGF treatment induced LIV‐1 mRNA by about 2‐fold whereas insulin increased expression only to a minor extent. The mRNA expression of E‐cadherin paralleled that of LIV‐1 with these treatments. MDA‐MB‐231 cells were also transfected with an shRNA construct designed to knock down LIV‐1 expression. This procedure reduced LIV‐1 mRNA concentrations by 30% and expression of E‐cadherin was reduced to a similar extent. This association between LIV‐1 and E‐cadherin expression in MDA‐MB‐231 cells suggests that LIV‐1 may be a regulator of E‐cadherin in both estrogen‐receptor positive and negative cells. The presence of LIV‐1 could serve as a prognostic marker for breast cancer patients with invasive tumors.